Major Cardiovascular Disease Events Research Articles

Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study

Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. For the Spanish translation of the abstract see Supplementary Materials section.

Sleep duration irregularity and risk for incident cardiovascular disease in the UK Biobank.

Emerging evidence supports a link between circadian disruption as measured by higher night-to-night variation in sleep duration and increased risk of cardiovascular disease (CVD). It remains unclear whether this association varies by CVD types or may be modified by average sleep duration and genetic risk for CVD. Our prospective analysis included 86,219 UK Biobank participants who were free from CVD when completing 7 days of accelerometer measurement in 2013-2016. Sleep irregularity was evaluated by the standard deviation (SD) of accelerometer-measured sleep duration over 7 days. Incident major CVD events, defined as fatal or nonfatal myocardial infarction (MI) and stroke, were identified through linkage to Hospital Episode Statistics data until May 31, 2022. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for associations of sleep duration SD with risk for major CVD events overall and for MI and stroke separately. We documented 2,310 incident cases of major CVD events (MI: 1,183, stroke: 1,175) over 636,258 person-years of follow-up. After adjusting for sociodemographic factors and family history of CVD, the HR (95% CI) associated with a 1-hour increase in sleep duration SD was 1.19 (1.10, 1.27) for CVD (p-trend<0.0001), 1.23 (1.11, 1.35) for MI (p-trend<0.0001), and 1.17 (1.05, 1.29) for stroke (p-trend=0.003). Additional adjustment for lifestyle factors, co-morbidities and sleep-related factors modestly attenuated these associations. Higher sleep irregularity was associated with higher CVD risk irrespective of genetic risk (p-interaction=0.43), but this association was stronger among individuals with longer average sleep duration >8 hours (p-interaction=0.006). Higher night-to-night variation in accelerometer-measured sleep duration was associated with consistently higher risks for major CVD events. The association did not seem to be modified by genetic risk for CVD and was more pronounced in long sleepers.

Interventions for primary prevention of cardiovascular disease: umbrella review of systematic reviews.

Cardiovascular diseases are the leading cause of death globally. The aim of this overview of systematic reviews was to compare the effectiveness of different pharmacological and non-pharmacological interventions for the primary prevention of cardiovascular disease. A structured search of the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and the Database of Abstracts of Reviews of Effects archive was conducted to find systematic reviews that reported the effect of various pharmacological and non-pharmacological interventions for the primary prevention of cardiovascular disease from inception to March 2021. References of included studies were also checked. The included systematic reviews' methodological quality was assessed using the Assessment of Multiple Systematic Reviews 2 instrument (range, 0-16). The outcomes of each included review's meta-analysis were extracted and described narratively. This study analysed 95 systematic reviews, including 41 on non-pharmacological interventions and 54 on pharmacological interventions for cardiovascular health. The majority of the reviews focused on lipid-lowering interventions (n = 25) and antiplatelet medications (n = 21), followed by nutritional supplements, dietary interventions, physical activity, health promotion and other interventions. Only 1 of the 10 reviews addressing cardiovascular mortality showed a potential benefit, while the others found no effect. Antiplatelets were found to have a beneficial effect on all-cause mortality in 2 out of 12 meta-analyses and on major cardiovascular disease events in 8 out of 17 reviews. Lipid-lowering interventions showed beneficial effects on cardiovascular disease mortality, all-cause mortality and major cardiovascular disease events in varying numbers of the reviews. Glucose-lowering medications demonstrated significant benefits for major cardiovascular events, coronary heart disease events and mortality. However, the combination of dietary interventions, physical activities, nutritional supplements and polypills showed little or no significant benefit for major cardiovascular outcomes or mortality. More research is needed to determine whether the effect of treatment varies depending on population characteristics. The findings of this review should be interpreted with caution because the majority of studies of non-pharmacological interventions compare primary prevention with usual care, which may include recommended pharmacological treatment in higher-risk patients (e.g. statins and/or antihypertensive medications, etc.). In addition, randomised controlled trial evidence may be better suited to the study of pharmacological interventions than dietary and lifestyle interventions. This umbrella review captured the variability in different interventions on randomised controlled trial evidence on interventions for primary prevention of cardiovascular disease and identified areas that may benefit from further research. Specifically, this review focused on randomised controlled trial evidence on interventions for primary prevention of cardiovascular disease. Researchers may use these findings as a resource to direct new intervention studies and network meta-analyses to compare the efficacy of various interventions based on these findings. This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment (HTA) programme as award number 17/148/05.

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

EFFECT OF ANTIHYPERTENSIVE DEPRESCRIBING ON SERIOUS ADVERSE EVENTS, MORTALITY, AND CARDIOVASCULAR DISEASE: LONG-TERM FOLLOW-UP OF THE OPTIMISE RANDOMISED CONTROLLED TRIAL

Objective: Deprescribing of antihypertensive medications is recommended for some older patients with polypharmacy and frailty. The OPTIMISE trial showed that this can be achieved without affecting blood pressure control at 3-month follow-up. This longer-term follow-up study aimed to examine the impact on serious adverse events (SAEs), mortality and cardiovascular disease (CVD) outcomes after at least 3 years. Design and method: Participants aged 80 years or older, with systolic blood pressure &lt;150 mmHg, and receiving at least 2 antihypertensive medications were randomised (1:1) to a strategy of antihypertensive medication reduction (removal of one antihypertensive) or usual care. Participants were followed-up via their primary and secondary care electronic health records, at least 3 years after randomisation. The primary outcome was SAEs, defined as hospitalisation or death from any cause. Secondary outcomes included mortality, stroke, myocardial infarction and major CVD events. Analyses were undertaken using Cox proportional hazards modelling. Results: Among 569 randomised participants (intervention=282; control=287) with a mean age 85 years (276 [48.5%] women), 564 (99.1%) were followed-up for a median of 3.9 years. Medication reduction was sustained in 109 participants (52.7% of those alive in the intervention group) at 3 years. Participants in the intervention group were prescribed fewer antihypertensives than the control group (mean difference -0.35, 95%CI -0.52 to -0.18). Overall, 202 (72.1%) patients in the intervention group and 218 (76.8%) patients in the control group experienced SAEs during follow-up (adjusted HR 0.93, 95%CI 0.76-1.12). There was no evidence of a difference in mortality (aHR 0.81, 95%CI 0.58-1.13), stroke (aHR 0.91, 95%CI 0.40-2.06), myocardial infarction (aHR 0.86, 95%CI 0.42-1.77) or CVD events (aHR 1.00, 95%CI 0.68-1.46). Conclusions: Medication reduction was sustained in half of those attempting it, with no evidence of harm from SAEs, mortality or CVD after almost four years. These findings suggest that deprescribing antihypertensive medication is safe in older patients living in the community with controlled blood pressure.

Associations of perceived built environment characteristics using NEWS questionnaires with all-cause mortality and major cardiovascular diseases: The prospective urban rural epidemiology (PURE)-China study

BackgroundDespite increased literature focusing on the role of the built environment (BE) in health, few cohort studies have quantitatively analyzed neighborhood walkability environment in relation to the risk of death and cardiovascular disease (CVD). This longitudinal study aimed at evaluating the association between perceived BE attributeswith mortality and major CVD based on the Prospective Urban Rural Epidemiology study in China (PURE-China). MethodsThe PURE-China study recruited 47,931 participants aged 35–70 years from 12 provinces of China between 2005 and 2009. The perceived BE information, including land use, street, aesthetics, and safety, was collected using the neighborhood environment walkability scale (NEWS) questionnaire, with higher scores indicating a more favorable rating. Two primary outcomes are all-cause mortality and major CVD event. The Cox frailty model with random intercepts was used to assess the association between the perceived total BE/subscales score and outcomes. ResultsOf 32,163 participants included in this study, 19,253 (59.9 %) were women, and the mean (SD) age was 51.0 (9.5) years. After a median follow-up period of 11.7 years (IQR 9.4 – 12.2), we observed that one standard deviation higher of combined BE scores was related to a lower risk of all-cause mortality (HR = 0.85; 95 %CI, 0.80–0.90), and major CVD events (HR = 0.95; 95 %CI, 0.90–0.99). The subscales of perceived BE were related to a lower risk, although a few were not significant. Land use mix-diversity and safety from crime were the two most significant subscales. Stronger risks were observed among urban and female participants. ConclusionFavorable perceived BE characteristics were linked with a lower risk of all-cause mortality and major CVD events in Chinese population, especially in urban areas and females. Our findings can be used by policymakers to take action to mitigate the adverse effect of poor community conditions on health, such as improving local amenities and transport connectivity, providing building paths for walking, running and cycling.

Loneliness, social isolation, and cardiovascular disease among nonveteran and veteran women

We examined the prospective associations of social isolation and loneliness with incident cardiovascular disease (CVD) among aging nonveteran and veteran women, and effect modification by veteran status. Participants with no history of myocardial infarction (MI), stroke, coronary heart disease (CHD), or coronary heart failure from the Women’s Health Initiative Extension Study II self-reported social isolation, loneliness, health behaviors, health status, and veteran status. CVD and CVD subevents were physician adjudicated. Hazard ratios (HR) and 95% confidence intervals (CI) for the Interquartile Range (IQR) in social isolation (IQR = 1) and loneliness (IQR=.33) were calculated using Cox proportional hazard models adjusting for sociodemographic, health behavior, and health status characteristics. Veteran status was tested as an effect modifier. Among 52,442 women (Mean age = 79 ± 6.1; veterans n = 1023; 89.2% non-Hispanic White), 3579 major CVD events occurred over an average 5.8 follow-up years. Compared to nonveterans, veteran women reported higher levels of social isolation (p < .01) and loneliness (p < .01). The CVD HR was 1.07 (95% CI, 1.04–1.10) for the IQR in social isolation and 1.03 (95% CI, 1.10–1.06) for the IQR in loneliness. The HR for the IQR in both social isolation and loneliness was 1.10 (95% CI, 1.05–1.15). Social isolation was associated with CHD (HR = 1.12; 95% CI, 1.03–1.21). The CHD HR for the IQR in social isolation was 1.12 (95% CI, 1.03–1.21). Associations did not differ by veteran status (all p-interactions > 0.08). Findings suggest that the adverse associations of social isolation and loneliness with CVD are similar among veteran and nonveteran women.

Associations of dietary copper intake with cardiovascular disease and mortality: findings from the Chinese Perspective Urban and Rural Epidemiology (PURE-China) Study

BackgroundPrevious in vitro and animal experiments have shown that copper plays an important role in cardiovascular health. Dietary copper is the main source of copper in the human body and the association between dietary copper and cardiovascular disease remains unclear. Our study aimed to investigate the associations of dietary copper intake with the risk of major cardiovascular disease incidence, cardiovascular disease mortality, and all-cause mortality in Chinese adults.MethodsOur study is based on Prospective Urban Rural Epidemiology China (PURE-China), a large prospective cohort study of 47 931 individuals aged 35–70 years from 12 provinces in China. Dietary intake was recorded using a validated semi-quantitative food frequency questionnaire designed specifically for the Chinese population. The daily intake of copper was obtained by multiplying the daily food intake with the nutrient content provided in the Chinese Food Composition Table (2002). Cox frailty proportional hazards models were developed to evaluate the association between dietary copper intake with mortality, major cardiovascular disease events, and their composite.ResultsA total of 45 101 participants (mean age: 51.1 ± 9.7 years old) with complete information were included in the current study. The mean dietary copper intake was 2.6 ± 1.1 mg/d. During the 482 833 person-years of follow-up, 2 644(5.9%) participants died, 4 012(8.9%) developed new cardiovascular diseases, and 5 608(12.4%) participants experienced the composite endpoint. Compared with those in the first and second quartile of dietary copper intake, individuals in the third and fourth quantile had higher risk of composite outcomes, all-cause death, cardiovascular disease death, major cardiovascular disease and stroke occurrences. The associations remained similar in the subgroup and sensitivity analyses.ConclusionsOur findings demonstrated that excessive dietary copper intake was associated with higher risks of death and cardiovascular diseases in Chinese adults. Further studies in populations with different dietary characteristics are needed to obtain dose–response relationships and to refine global dietary recommendations.

Abstract 15439: Association of Vigorous Physical Activity With Cardiovascular Disease and Mortality in 136,766 Adults From High-Income, Middle-Income and Low-Income Countries: The Prospective Urban Rural Epidemiological (PURE) Study

Background: It’s recommended adults get 150-300 minutes of moderate physical activity (MPA) and/or 75-150 minutes of vigorous physical activity (VPA) per week. Some studies have found high VPA to be protective and others found it to be harmful. These studies have been conducted in high-income countries using recreational VPA as the exposure of interest. Purpose: To evaluate the effects of VPA with all-cause mortality, and cardiovascular disease (CVD) in countries at different economic levels. Methods: Participants aged 35-70 years were recruited from 21 countries at various stages of economic development. Physical activity (total, walking, MPA, VPA, as well as recreational vs. non-recreational PA) was assessed using the International Physical Activity Questionnaire. Primary clinical outcomes were the composite of mortality plus major CVD (CVD mortality, myocardial infarction, stroke, or heart failure) and mortality. A total of 136,766 participants without baseline CVD, cancer, and HIV were analyzed. Models were adjusted for age, sex, urban/rural residency, country income level, education, household wealth index, smoking, baseline chronic diseases, physical impairments, MPA, walking and centre as a random effect. Results: During the median follow-up of 11.5 (8.6-12.4) years, there were 9846 deaths and 7900 major CVD events. The median min/wk (IQR) for total PA, walking, MPA and VPA were 690 (250-1530), 40 (0-420), 330 (75-860), 0 (0-0). The mean VPA was 103±390 min/wk. Compared to no VPA, 150-299 minutes per week of VPA was associated with reduced risk for the composite outcome and mortality, HR = 0.82 (0.73,0.92) and 0.74 (0.64,0.86), respectively. When VPA was stratified into either recreational or non-recreational VPA, recreational VPA displayed a U-shape relationship, such that higher levels were associated with less benefit. Increasing non-recreational VPA continued to confer reduced risk even above 3000 min/wk. At any amount of moderate PA, higher VPA was associated with reduced risk for the composite outcome and mortality. Conclusion: Higher levels of VPA were associated with reduced risk for mortality and major CVD events up to more than 40 times the minimum recommended amount. At no point did VPA confer an increased risk.

Abstract 13282: Parental Allostatic Load Predicts Time to the Onset of Cardiovascular Disease in Offspring

Background: Allostatic load, a measure of cumulative stress-related physiologic dysregulation, is associated with major cardiovascular disease (CVD) events. However, despite evidence of familial aggregation of CVD risk factors, the impact of parental allostatic load on the onset and timing of CVD in offspring remains unknown. Hypothesis: We hypothesize that offspring of parents with lower allostatic load will have longer CVD-free survival time. Aim: To examine whether CVD-free survival in offspring is associated with parental allostatic load and potential sex-specific differences. Methods: A secondary data analysis of 6,145 offspring-mother-father trios derived from the Framingham Heart Study Original (exam 10) and Offspring Cohorts (exam 1). Allostatic load was defined as an index (0-16) of 8 variables (systolic and diastolic blood pressure, total cholesterol, HDL, LDL, total cholesterol/ HDL ratio, fasting blood glucose and body mass index). Kaplan-Meier plots, and Irwin’s restricted mean and multivariable-adjusted Cox proportional hazards regression models were used to examine sex-specific differences and the association between parental allostatic load and offspring’s CVD-free survival. Results: Parents mean age (SD) was 60.8 (8.1) and offspring’s 34.8 (10.5). 22.8% of parents (n=458) and 12.1% (n=412) of offspring had high allostatic load (&gt;8). In a total of 118,132 person-years of follow-up among the offspring, 1060 incident CVD events occurred. The overall CVD incidence rate was 8.9 per 1000 person-years (95% confidence interval [CI] 8.4-9.5) and sons had a higher CVD incident rate than daughters (11.0 vs 7.2, p&lt;0.001). Offspring of mothers with low allostatic load lived 4 more years free of CVD compared to offspring of mothers with high allostatic load. Similarly, offspring of fathers with low allostatic load lived 3 more years free of CVD. The hazard rate of having incident CVD among offspring of mothers and fathers with high (compared to low) allostatic load was 1.58 (1.28-1.95) and 1.39 (95% CI: 1.11-1.75), respectively. Conclusion: Parents' allostatic load has a significant impact on the cardiovascular health of their offspring, with those of mothers with high allostatic load being at a higher risk of developing CVD at a younger age.

Long-term comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events: a population-based retrospective inception cohort study in the Netherlands

ObjectiveTo determine the long-term effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events.DesignRetrospective inception cohort study covering a 25-year study period.SettingUniversity Groningen IADB.nl pharmacy prescription database with data from...

Quantifying COPD as a risk factor for cardiac disease in a primary prevention cohort.

Despite COPD being a risk factor for cardiovascular disease (CVD) and knowing that risk stratification for CVD primary prevention is important, little is known about the real-world risk of CVD among people with COPD with no history of CVD. This knowledge would inform CVD management for people with COPD. The current study aimed to examine the risk of major adverse cardiovascular events (MACE) (including acute myocardial infarction, stroke or cardiovascular death) in a large, complete real-world population with COPD without previous CVD. We conducted a retrospective population cohort study using health administrative, medication, laboratory, electronic medical record and other data from Ontario, Canada. People without a history of CVD with and without physician-diagnosed COPD were followed between 2008 and 2016, and cardiac risk factors and comorbidities compared. Sequential cause-specific hazard models adjusting for these factors determined the risk of MACE in people with COPD. Among ∼5.8 million individuals in Ontario aged ≥40 years without CVD, 152 125 had COPD. After adjustment for cardiovascular risk factors, comorbidities and other variables, the rate of MACE was 25% higher in persons with COPD compared with those without COPD (hazard ratio 1.25, 95% CI 1.23-1.27). In a large real-world population without CVD, people with physician-diagnosed COPD were 25% more likely to have a major CVD event, after adjustment for CVD risk and other factors. This rate is comparable to the rate in people with diabetes and calls for more aggressive CVD primary prevention in the COPD population.

Liver disease is a significant risk factor for cardiovascular outcomes – A UK Biobank study

Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events. Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c). A total of 33,616 participants (mean age 65 years, mean BMI 26kg/m2, mean haemoglobin A1c 35mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p= 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p= 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p= 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001). Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat. Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.

Severe Mental Illness and Type 2 Diabetes Outcomes and Complications: A Nationwide Cohort Study.

To compare cardiovascular and mortality outcomes in people with severe mental illness (SMI) versus no mental illness in a national cohort study of people with type 2 diabetes. We included adults diagnosed with type 2 diabetes between 2004 and 2018 from the national Scottish diabetes register, ascertaining history of mental illness from linked psychiatric and general hospital admission records. We identified major cardiovascular disease (CVD) events, all-cause mortality, and CVD-specific mortality through record linkage. Using Cox regression, we estimated hazard ratios (HRs) for associations between SMI and outcomes, adjusting for baseline sociodemographic and clinical characteristics, including history of CVD, comorbidity, hypertension, high cholesterol, HbA1c, BMI, alcohol use disorder, and smoking. Among 259,875 people with type 2 diabetes, 1.0%, 0.5%, and 3.0% had schizophrenia, bipolar disorder, and major depression, respectively. After adjusting for sociodemographic characteristics, the risk of major CVD events was higher in people with schizophrenia (HR 1.22, 95% CI 1.06-1.41), bipolar disorder (HR 1.58, 95% CI 1.33-1.87), and major depression (HR 1.59, 95% CI 1.49-1.70) compared with people without a history of mental illness. SMI was also associated with an approximately twofold increased risk of CVD-specific and all-cause mortality. All associations attenuated following further adjustment for clinical characteristics. Among people with diabetes, people with a history of SMI have poorer cardiovascular and mortality outcomes compared with those without mental illness. While the underlying mechanisms are further investigated, effective prevention and management of cardiovascular risk factors is needed in this high-risk group.

Clinical outcomes of renin angiotensin system inhibitor-based dual antihypertensive regimens in chronic kidney disease: a network meta-analysis

This study comprehensively investigated clinical outcomes associated with renin angiotensin system inhibitor-based dual antihypertensive regimens in non-dialysis chronic kidney disease (CKD) patients. Keyword searches of databases were performed per PRISMA-NMA guidelines. Frequentist network meta-analysis were conducted with 16 head-to-head randomized controlled trials. The effect sizes of dichotomous and continuous variables were estimated with odds ratio (OR) and standard mean differences (SMD), respectively. The protocol is registered in PROSPERO (CRD42022365927). Dual antihypertensive regimens with combination of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) demonstrated substantially reduced odd of major cardiovascular disease (CVD) events over other regimens including angiotensin converting enzyme inhibitor (ACEI) monotherapy (OR 3.19) and ARB monotherapy (OR 2.64). Most significant reductions in systolic (SBP) and diastolic blood pressure (DBP) were observed with ARB-based CCB dual regimen over ACEI monotherapy (SMD 17.60 SBP and 9.40 for DBP), ACEI-based CCB regimen (SMD 12.90 for SBP and 9.90 for DBP), and ARB monotherapy (SMD 13.20 for SBP and 5.00 for DBP). However, insignificant differences were noticed for the odds of hyperkalemia, end stage renal disease progression, and all-cause mortality. ARB-based CCB regimen has the greatest benefits on BP reduction as well as major CVD risks in non-dialysis CKD patients.

Acute Coronary Syndrome, Stroke, and Mortality after Community-Acquired Pneumonia: Systematic Review and Meta-Analysis

One-third of adult inpatients with community-acquired pneumonia (CAP) develop acute coronary syndrome (ACS), stroke, heart failure (HF), arrhythmias, or die. The evidence linking CAP to cardiovascular disease (CVD) events is contradictory. We aimed to systematically review the role of CAP as a CVD risk factor. We registered the protocol (CRD42022352910) and searched for six databases from inception to 31 December 2022. We included 13 observational studies, 276,109 participants, 18,298 first ACS events, 12,421 first stroke events, 119 arrhythmic events, 75 episodes of new onset or worsening HF, 3379 deaths, and 218 incident CVD events. CAP increased the odds of ACS (OR 3.02; 95% CI 1.88-4.86), stroke (OR 2.88; 95% CI 2.09-3.96), mortality (OR 3.22; 95% CI 2.42-4.27), and all CVD events (OR 3.37; 95% CI 2.51-4.53). Heterogeneity was significant (I2 = 97%, p < 0.001). Subgroup analysis found differences according to the continent of origin of the study, the follow-up length, and the sample size (I2 > 40.0%, p < 0.10). CAP is a significant risk factor for all major CVD events including ACS, stroke, and mortality. However, these findings should be taken with caution due to the substantial heterogeneity and the possible publication bias.

Severe Infection and Risk of Cardiovascular Disease: A Multicohort Study.

The excess risk of cardiovascular disease associated with a wide array of infectious diseases is unknown. We quantified the short- and long-term risk of major cardiovascular events in people with severe infection and estimated the population-attributable fraction. We analyzed data from 331 683 UK Biobank participants without cardiovascular disease at baseline (2006-2010) and replicated our main findings in an independent population from 3 prospective cohort studies comprising 271 329 community-dwelling participants from Finland (baseline 1986-2005). Cardiovascular risk factors were measured at baseline. We diagnosed infectious diseases (the exposure) and incident major cardiovascular events after infections, defined as myocardial infarction, cardiac death, or fatal or nonfatal stroke (the outcome) from linkage of participants to hospital and death registers. We computed adjusted hazard ratios (HRs) and 95% CIs for infectious diseases as short- and long-term risk factors for incident major cardiovascular events. We also calculated population-attributable fractions for long-term risk. In the UK Biobank (mean follow-up, 11.6 years), 54 434 participants were hospitalized for an infection, and 11 649 had an incident major cardiovascular event at follow-up. Relative to participants with no record of infectious disease, those who were hospitalized experienced increased risk of major cardiovascular events, largely irrespective of the type of infection. This association was strongest during the first month after infection (HR, 7.87 [95% CI, 6.36-9.73]), but remained elevated during the entire follow-up (HR, 1.47 [95% CI, 1.40-1.54]). The findings were similar in the replication cohort (HR, 7.64 [95% CI, 5.82-10.03] during the first month; HR, 1.41 [95% CI, 1.34-1.48] during mean follow-up of 19.2 years). After controlling for traditional cardiovascular risk factors, the population-attributable fraction for severe infections and major cardiovascular events was 4.4% in the UK Biobank and 6.1% in the replication cohort. Infections severe enough to require hospital treatment were associated with increased risks for major cardiovascular disease events immediately after hospitalization. A small excess risk was also observed in the long-term, but residual confounding cannot be excluded.

Family History of Modifiable Risk Factors and Association With Future Cardiovascular Disease.

Background A parental history of cardiovascular disease (CVD) confers greater risk of future CVD among offspring. Whether the presence of parental modifiable risk factors contribute to or modify CVD risk in offspring is unclear. Methods and Results We studied 6278 parent-child trios in the multigenerational longitudinal Framingham Heart Study. We assessed parental history of CVD and modifiable risk factors (smoking, hypertension, diabetes, obesity, and hyperlipidemia). Multivariable Cox models were used to evaluate the association of parental history and future CVD among offspring. Among 6278 individuals (mean age 45±11 years), 44% had at least 1 parent with history of CVD. Over a median follow-up of 15 years, 353 major CVD events occurred among offspring. Parental history of CVD conferred 1.7-fold increased hazard of future CVD (hazard ratio[HR], 1.71 [95% CI, 1.33-2.21]). Parental obesity and smoking status were associated with higher hazard of future CVD (obesity: HR, 1.32 [95% CI, 1.06-1.64]; smoking: HR, 1.34 [95% CI, 1.07-1.68], attenuated after adjusting for offspring smoking status). By contrast, parental history of hypertension, diabetes, and hypercholesterolemia were not associated with future CVD in offspring (P>0.05 for all). Furthermore, parental risk factors did not modify the association of parental CVD history on future offspring CVD risk. Conclusions Parental history of obesity and smoking were associated with a higher hazard of future CVD in offspring. By contrast, other parental modifiable risk factors did not alter offspring CVD risk. In addition to parental CVD, the presence of parental obesity should prompt a focus on disease prevention.

1026 MYOCARDIAL INFARCTION AND STROKE IN A YOUNG PATIENT AFFECTED BY LES: KEY ROLE OF AN INTEGRATED IMAGING APPROACH

Abstract A male patient, 33 years old, smoker, with a 20-year history of SLE, consulted the ER for right hand fatigue. He didn't assume his medications constantly. Computed Tomography showed a fronto-parieto-occipital cerebral infarction, and the angio-CT showed a plaque in left internal carotid artery. The patient was admitted to the Stroke Unit for minor ischemic stroke. The ECG showed pathological Q waves in the anterior leads from V1 to V4 revealing a likely previous silent myocardial infarction. The echocardiogram demonstrated moderate left ventricular dysfunction with 40% EF and segmental wall motion abnormalities, namely ipoakinesia of anterior wall and apex. This findings were confirmed by cardiac MRI highliting subendocardial LGE in these areas suggesting an ischemic genesis. Due to the hemorrhagic risk related to recent cerebral ischemic event, coronary angiography was postponed a month later. The coronary angiography revealed a significant stenosis of the proximal left anterior descending artery (iFR &amp;lt; 0.65). Qualitative assessment of the lesion with IVUS showed a “mixed” plaque. The lesion was treated with PCI and the implant of two overlapped DES and the patient underwent dual antiplatelet therapy. Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with heterogeneous presentation, characterised by alternating periods of flares and remission, and irreversible organ damage. The skin, joints, heart, kidneys, central nervous system and haematologic system are some of the most affected organs. Although recent data suggest that mortality decreased in patients with SLE over the last 30 years, mortality due to cardiovascular disease (CVD), usually defined as a combination of coronary, cerebrovascular and/or peripheral arterial disease, has remained high. Stroke and myocardial infarction (MI) are major CVD events that are potentially life-threatening. Lupus specific cardiovascular risk factors are believed to contribute to the high risk for MI, such as renal involvement, that has been associated with increased subclinical atherosclerosis and ischaemic heart disease, and antiphospholipid syndrome (APS), defined by venous, arterial or small vessel thrombosis and/or obstetric complications together with persistent positivity for antiphospholipid antibodies (aPL). Though several risk factors have been suggested, the exact mechanisms behind the high MI incidence in SLE remain essentially unknown. MIs in SLE are in most cases associated with coronary atherosclerosis. Subclinical atherosclerosis has been reported in many case–control studies, but a direct causal relationship between coronary artery disease (CAD) and MI in SLE has not yet been well documented. The pathogenesis of cardiovascular diseases in SLE is not fully understood. The inflammatory nature of SLE is believed to be an important factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, promotes endothelial dysfunction and vascular injury. Our case showed the key role of an integrated imaging approach with echocardiography and cardiac MRI to confirm diagnosis of past myocardial infarction in a very young man affected by LES. IVUS played a great role to characterize the nature of the lesion, confirming the association between coronary atherosclerosis and MIs in SLE.

The design and development of an encounter tool to support shared decision making about preventing cardiovascular events

Patients at high risk for cardiovascular disease (CVD) tend to receive less intensive preventive care. Clinical practice guidelines recommend shared decision making (SDM) to improve the quality of primary CVD prevention. There are tools for use during the clinical encounter that promote SDM, but, to our knowledge, there are no SDM encounter tools that support conversations about available lifestyle and pharmacological options that can lead to preventive care that is congruent with patient goals and CVD risk.Using the best available evidence and human-centered design (iterative design in the context of ultimate use with users), our team developed a SDM encounter tool, CV Prevention Choice. Each subsequent version during the iterative development process was evaluated in terms of content, usefulness, and usability by testing it in real preventive encounters. The final version of the tool includes a calculator that estimates the patient’s risk of a major atherosclerotic CVD event in the next 10 years. Lifestyle and medication options are presented, alongside their pros, cons, costs, and other burdens. The risk reduction achieved by the selected prevention program is then displayed to support collaborative deliberation and decision making.A U.S. multicenter trial is estimating the effectiveness of CV Prevention Choice in achieving risk-concordant CV prevention while identifying the best strategies for increasing the adoption of the SDM encounter tool and its routine use in practice.